(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2010/0168049 A1
`(43) Pub. Date:
`Jul. 1, 2010
`LABOUREAU et al.
`
`US 201001 68049A1
`
`(54) COMBINATION OF MONOSACCHARIDES
`AND ADENOSINE AND USE THEREOF
`
`(75) Inventors:
`
`Julien LABOUREAU, Issy Les
`Moulineaux (FR); Jean-Thierry
`Simonnet, Cachan (FR); Pascal
`Portes, Nogent Sur Marne (FR)
`
`Correspondence Address:
`OBLON, SPIVAK, MCCLELLAND MAIER &
`NEUSTADT, L.L.P.
`194O DUKE STREET
`ALEXANDRIA, VA 22314 (US)
`
`(73) Assignee:
`
`LOREAL, Paris (FR)
`
`(21) Appl. No.:
`
`12/649,367
`
`(22) Filed:
`
`Dec. 30, 2009
`
`Related U.S. Application Data
`(60) Provisional application No. 61/144,756, filed on Jan.
`15, 2009.
`Foreign Application Priority Data
`
`(30)
`
`Dec. 30, 2008 (FR) ...................................... O8591.51
`Publication Classification
`
`(51) Int. Cl.
`(2006.01)
`A6IR 8/49
`(2006.01)
`A61O 19/00
`(52) U.S. Cl. .......................................................... 514/46
`(57)
`ABSTRACT
`The present invention relates to a composition, especially a
`cosmetic and/or dermatological composition, containing, in a
`physiologically acceptable medium, a combination of at least
`one monosaccharide chosen from mannose, rhamnose and a
`mixture thereof, and of at least one additional compound
`chosen from adenosine, an analogue thereof and a mixture
`thereof.
`
`UNIVERSITY OF MASSACHUSETTS - EX. 2002
`
`

`

`Patent Application Publication
`
`Jul. 1, 2010 Sheet 1 of 2
`
`US 2010/01 68049 A1
`
`Proliferation index on control in defined medium deficient in
`growth factors - treatment by L-rhamnose
`
`200 - - - - - - -
`
`-
`
`-
`
`- - - - - - - - - - -
`
`- - - - -r
`
`wr-
`
`- -
`
`- -
`
`wrv vv.
`
`--
`
`s
`5
`
`d
`-
`is
`
`i 5
`
`U
`
`s
`
`XTT
`a) Nile Red
`Cyguant
`
`175
`
`150
`
`125 -
`
`100 - -
`
`75
`
`50
`
`25 -
`
`O
`
`X X
`X
`4
`
`0 0
`KY X
`
`
`
`
`
`88:
`X
`4
`{ {
`88:
`X
`X X
`X X
`-
`X-X-
`
`Control
`
`100M
`
`500M
`
`1000M
`
`FIGURE 1
`
`Proliferation index on control in defined medium deficient in
`growth factors - treatment by D-mannose
`
`XTT
`at Nile Red
`Cyguant
`
`200
`
`175
`
`150 -
`
`125
`100 - -
`
`75 -
`
`50 -
`
`25
`
`O
`
`
`
`-
`
`E.
`X X
`d
`
`
`
`X
`88:
`0 0
`88:
`-
`AA
`
`FIGURE 2
`
`

`

`Patent Application Publication
`
`Jul. 1, 2010 Sheet 2 of 2
`
`US 2010/01 68049 A1
`
`Count of dermal fibroblasts on reconstructed skin
`
`3. O O
`
`2 5 O
`
`2 O O
`
`150
`
`100
`
`5 O
`
`
`
`Control
`
`Rhamnose 5 mM
`
`FIGURE 3
`
`Image 1: Control 120h
`
`Image 2 : Rhamnose 1 nM 120h
`
`FIGURE 4
`
`

`

`US 2010/01 68049 A1
`
`Jul. 1, 2010
`
`COMBINATION OF MONOSACCHARDES
`AND ADENOSINE AND USE THEREOF
`
`REFERENCE TO PRIORAPPLICATIONS
`0001. This application claims priority to U.S. provisional
`application Ser. No. 61/144,756, filed Jan. 15, 2009; and to
`French patent application 0859151, filed Dec. 30, 2008, both
`incorporated herein by reference.
`
`BACKGROUND OF THE INVENTION
`0002 The present invention relates to a composition,
`especially a cosmetic and/or dermatological composition,
`comprising, in a physiologically acceptable medium, a com
`bination of at least one monosaccharide selected from man
`nose, rhamnose and a mixture thereof, and of at least one
`additional compound selected from adenosine, an analogue
`thereof and a mixture thereof.
`0003. Additional advantages and other features of the
`present invention will be set forth in part in the description
`that follows and in part will become apparent to those having
`ordinary skill in the art upon examination of the following or
`may be learned from the practice of the present invention. The
`advantages of the present invention may be realized and
`obtained as particularly pointed out in the appended claims.
`As will be realized, the present invention is capable of other
`and different embodiments, and its several details are capable
`of modifications in various obvious respects, all without
`departing from the present invention. The description is to be
`regarded as illustrative in nature, and not as restrictive.
`
`BACKGROUND OF THE INVENTION
`0004 Human skin is made up of two main layers, namely
`the dermis and the epidermis that superficially covers the
`dermis. Natural human epidermis is composed mainly of
`three types of cells, namely keratinocytes, which form the
`vast majority, melanocytes and Langerhans cells. Each of
`these three types of cells contributes, via its intrinsic func
`tions, to the essential role played in the body by the skin,
`especially the role of protecting the body against external
`attacking factors (the climate, ultraviolet rays, tobacco, etc.),
`which is also known as the “barrier function'.
`0005. The epidermis is a keratinized, stratified pavement
`epithelium 90% made up of keratinocytes. The gradual dif
`ferentiation of the cells of the basal membrane, which sepa
`rates the dermis from the epidermis, towards the surface of the
`epidermis especially includes the differentiation of kerati
`nocytes, which migrate towards the Surface of the skin, where
`they descquamate.
`0006 Ageing of the epidermis is manifested mainly by a
`reduction in its thickness. Atrophy of the epidermis is the
`consequence of the slowing down of keratinocyte prolifera
`tion and of the accumulation of senescent keratinocytes. The
`horny layer becomes dull.
`0007. The dermis provides the epidermis with a solid Sup
`port. It is also its nourishing element. It is made up mainly of
`fibroblasts and an extracellular matrix composed mainly of
`collagen, elastin and a substance known as ground Substance.
`These components are synthesized by the fibroblasts. The
`cohesion between the epidermis and the dermis is provided by
`the dermo-epidermal junction. This is a complex region about
`100 nm thick, which comprises the basal pole of the basal
`keratinocytes, the epidermal membrane and the Sub-basal
`Zone of the superficial dermis.
`0008 Collagens are the major proteins of the extracellular
`matrices of the skin. To date, 20 types of collagen have been
`identified, and are noted from I to XX. The collagens pre
`
`dominantly present throughout the epidermis are collagens of
`the type I and III that form the extracellular matrix of the
`entire dermis (these collagens constitute 70-80% of the dry
`weight of the dermis). Moreover, collagens are not all Syn
`thesized by the same cell types: collagens of type I and III are
`essentially produced by the dermal fibroblasts, whereas type
`VII collagen is produced by two categories of cell, kerati
`nocytes and fibroblasts. Regulation of their expression differs
`from one collagen to another, for example collagens I and VII
`are not regulated in the same way by certain cytokines; spe
`cifically, TNF-C. and leukoregulin stimulate collagen VII and
`negatively regulate collagen I. Finally, all collagen molecules
`are variants of a common precursor, which is the C. chain of
`procollagen.
`0009. With age, collagen becomes thinner and wrinkles
`appear on the Surface of the skin. Cutaneous ageing is a
`genetically programmed mechanism.
`0010 Moreover, certain environmental factors such as
`Smoking and above all exposure to Sunlight accelerate it. The
`skin thus has a much more aged appearance on the areas
`exposed to Sunlight, such as the back of the hands or the face.
`Thus, these other factors also have a negative impact on the
`natural collagen of the skin.
`0011 Consequently, given the important role of collagen
`in the integrity of the skin and in its resistance to external
`attacking factors of mechanical type, Stimulation of the Syn
`thesis of these collagens, and in particular of type I collagen,
`appears to be an effective means for overcoming the signs of
`ageing of the skin. During chronological and/or actinic age
`ing, the epidermis also undergoes many changes and degra
`dations that are reflected, with age, by an impairment in the
`microrelief, impairment in the barrier function of the skin, the
`appearance of wrinkles and fine lines, an impairment in the
`mechanical properties of the skin, especially lack of elasticity
`of the skin, and loss of radiance of the complexion.
`0012 Expression wrinkles are the result of mechanisms
`different from those that generate the wrinkles caused by
`ageing. Specifically, they are produced due to the effect of the
`strain exerted on the skin by the skin muscles that allow facial
`expressions. Depending on the shape of the face, the fre
`quency of facial expressions and possible tics, they may
`appear even from childhood. Expression wrinkles are char
`acterized by the presence of grooves around the orifices
`formed by the nose (nasal grooves), the mouth (perioral
`wrinkles and “sour-face' wrinkles) and the eyes (crow's-feet
`wrinkles), around which are the skin muscles, and also
`between the eyebrows (glabella wrinkles or lion wrinkles)
`and on the forehead.
`0013 Hitherto, the only means commonly used for acting
`on expression wrinkles are, firstly, botulinum toxin, which is
`especially injected into the wrinkles of the glabella which are
`wrinkles between the eyebrows (see J. D. Carruters et al., J.
`Dermatol. Sum. Oncol., 1992, 18, pp. 17-21), and, secondly,
`degradable implants based on collagen, hyaluronic acid or
`polylactic acid.
`0014. The importance of having available compositions
`whose effects are directed towards regenerating skin tissue
`via increasing keratinocyte proliferation and stimulating
`fibroblast proliferation and/or metabolism, and especially
`stimulating the synthesis of procollagens and collagens, and
`also for combating cutaneous contractions that are respon
`sible for the formation of expression wrinkles, may thus be
`appreciated.
`0015. It is known practice from the literature to use agents
`Such as retinol, which promote keratinocyte proliferation and
`can stimulate epidermal renewal and maintain and/or
`increase the thickness of the epidermis: this is then referred to
`
`

`

`US 2010/01 68049 A1
`
`Jul. 1, 2010
`
`thereof. As described previously, this is the combination of a
`biological action and a mechanical action, the latter being
`intended to tighten and constrain the skin.
`(0024 Patent application WO 2005/063194 describes a
`galenical base with very high tolerance especially comprising
`mannose or rhamnose. It is specified that Such a galenical
`base can function only in combination with an active agent of
`which it is only the vehicle. The dermal and/or cosmetic
`galenical bases disclosed are based essentially on the pres
`ence of the two polyols, namely mannitol and Xylitol.
`0025. Moreover, the influence of adenosine and adenosine
`analogues on improving the appearance of the skin is
`described in patent applications EP 1 424064 and EP 1 428
`522. In particular, it is specified therein that adenosine makes
`it possible to relax or decontract the dermal contractile cells
`that are assumed to be involved in the generation of expres
`sion wrinkles.
`0026. The present invention thus relates in one embodi
`ment to a composition, especially a cosmetic and/or derma
`tological composition, comprising, in a physiologically
`acceptable medium, a combination of at least one monosac
`charide chosen from mannose and rhamnose and of at least
`one additional compound chosen from adenosine and adenos
`ine analogues.
`0027. The monosaccharides according to the invention are
`in the D or L form of mannose and/or rhamnose, each form
`itself possibly being the alpha and/or beta anomer. The forms
`that are preferred according to the invention are D-mannose
`and L-rhamnose.
`0028 D-Mannose is present in plants, in particular certain
`fruit, including cranberries, or inhardwood (beech and birch).
`Rhamnose is found in nature in L form. D-Mannose and
`L-rhamnose are commercially available, for example from
`the companies Danisco Sweeteners(R and Symrise.
`0029. In the present invention, the monosaccharide is pref
`erably present as a monomer.
`0030. For the purposes of the present invention, adenosine
`is the nucleoside derived from the condensation of adenine
`with ribose (in ribofuranose form) via B-Noglucoside bond.
`Adenosine plays an important role in biochemical processes,
`Such as energy transfer when it is, for example, in the form of
`adenosine triphosphate (ATP) and/or adenosine diphosphate
`(ADP), and also in signal transduction when it is, for
`example, in the form of cyclic adenosine monophosphate or
`cAMP. Adenosine has the following structural formula:
`
`NH2
`
`as a direct biological effect. However, retinol has a certain
`number of drawbacks when it is used in a cosmetic compo
`sition. Specifically, it has low stability towards oxidation and
`gives rise to adverse side effects on consumers, especially
`such as skin irritation. There is thus a need to find other
`compounds with a direct biological effect, which are readily
`available and whose efficacy is acceptable for optimal use in
`cosmetics.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`0016 FIG. 1 shows the results obtained for the kerati
`nocyte proliferation under certain conditions, described in
`detail below.
`0017 FIG. 2 shows the results obtained for the kerati
`nocyte proliferation under certain conditions, described in
`detail below.
`0018 FIG. 3 shows the number of fibroblasts measured
`between an untreated control whole reconstructed skin, on the
`left, and a whole reconstructed skin treated with 5 mM of
`rhamnose, on the right.
`0019 FIG. 4 shows images of frozen sections of recon
`structed skin 7 um thick.
`
`DETAILED DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`0020. The inventors have discovered, surprisingly and
`unexpectedly, that a combination of at least one monosaccha
`ride selected from mannose, rhamnose and a mixture thereof,
`and of at least one additional compound selected from
`adenosine, an adenosine analogue and mixtures thereof, leads
`to a complementarity of action both on the microrelief of the
`skin, making it possible especially to combat the formation of
`expression wrinkles, and also on the stimulation of dermal
`and/or epidermal regeneration by stimulating the metabolism
`and the process of epidermal renewal, leading to a reduction
`in the appearance of the signs of chronological ageing and
`photoageing. Thus, the combination according to the inven
`tion causes relaxation, decontraction and a reduction in the
`differentiation of the dermal contractile cells involved in the
`generation of expression wrinkles, especially of the fibro
`blasts located along the tension lines created under the effect
`of contraction of the skin muscles. The combination accord
`ing to the invention also makes it possible to synergistically
`stimulate the production of type I procollagen by the dermal
`fibroblasts.
`0021. As used herein the term “synergistic' and its deriva
`tives means a greater than additive effect.
`0022. The present invention demonstrates the activation of
`keratinocyte and fibroblast proliferation and the stimulation
`of procollagen I synthesis by mannose or rhamnose. The use
`of compositions containing them thus makes it possible to
`counter the signs of ageing of the skin, and in particular
`age-related epidermal and/or dermal atrophy.
`0023 The use of these monosaccharides for the direct
`biological effects outlined above was hitherto unknown.
`Patent application WO 2007/128 939 mentions, however,
`anti-ageing activity obtained via a biomechanical effect of a
`tensioning agent in combination with saccharide compounds,
`which make it possible to increase the expression of the skin
`cell mechanoreceptors. This increase in the expression of
`mechanoreceptors is described as increasing the sensitization
`of skin cells to respond to the effects of tensioning agents.
`Similarly, patent application FR 2 900 572 describes the
`combined use of a cosmetic composition comprising saccha
`ride compounds and a device for applying mechanical con
`straints to the skin, in order to improve the homeostasis
`
`HO
`
`N
`
`N
`
`O
`
`{l
`
`n N
`
`2
`N
`
`OH OH
`
`0031. Among the adenosine analogues that may be used
`according to the invention, mention will be made especially
`of adenosine receptor agonists and compounds that increase
`the intracellular or extracellular levels of adenosine.
`0032 Examples of adenosine analogues include:
`2'-deoxyadenosine; 2',3'-isopropylideneadenosine; toyoca
`
`

`

`US 2010/01 68049 A1
`
`Jul. 1, 2010
`
`mycin; 1-methyladenosine; N-6-methyladenosine; adenos
`ine N-oxide: 6-methylmercaptopurine riboside and 6-4 chlo
`ropurine riboside.
`0033. Other adenosine analogues include adenosine
`receptor agonists, including phenylisopropyladenosine
`(PIA).
`1-methylisoguanosine, N6-cyclohexyladenosine
`(CHA), N6-cyclopentyladenosine (CPA), 2-chloro-N6-cy
`clopentyladenosine, 2-chloroadenosine, N6-phenyladenos
`ine, 2-phenylaminoadenosine, MECA, N6-phenethyladenos
`ine,
`2-p-(2-carboxyethyl)phenethylamino-5'-N-
`ethylcarboxamidoadenosine
`(CGS-21680),
`N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)
`carboxamidoadenosine, DPMA (PD 129,944) and metrifudil.
`0034 Among the adenosine analogues that increase the
`intracellular adenosine concentration in the composition
`according to the invention, the compounds included in the
`group formed by erythro-9-(2-hydroxy-3-nonyl)-adenine
`(EHNA) and iodotubercidine are preferred.
`0035. The adenosine analogues may also be compounds of
`formula (I) below:
`
`OR
`
`O
`
`RO
`
`OR
`
`(I)
`
`NH2
`
`o N
`
`?
`
`2
`\
`Ns
`
`0036 in which:
`0037 R1 and R2, which are identical, denote a linear
`saturated C1-C6 or unsaturated C2-C6, or branched saturated
`or unsaturated C3-C6 hydrocarbon-based radical, or alterna
`tively form, together with the oxygenatoms to which they are
`attached, an isopropylidene radical;
`0038 R3 denotes:
`0039 (i) a linear saturated C1-C10 or unsaturated
`C2-C10, or branched saturated or unsaturated C3-C10 hydro
`carbon-based radical, optionally substituted with at least one
`group chosen from OR', NR'R", COOR, CONR'R",
`CF3, - F - OCF3, CN and NO2, or
`0040 (ii) a group—COR4 with R4 denoting a linear satu
`rated C1-C9 or unsaturated C2-C9, or branched saturated or
`unsaturated C3-C9 hydrocarbon-based radical, optionally
`substituted with at least one group chosen from —OR',
`NR'R'', COOR, CONR'R'',
`CF3,
`F,
`OCF3,
`–CN and - NO2; or
`0041
`(iii) a biotin-based ester group:
`0042 R and R" denoting a hydrogen atom, a linear satu
`rated C1-C6 or unsaturated C2-C6, or branched saturated or
`unsaturated C3-C6 hydrocarbon-based radical, optionally
`Substituted with at least one group chosen from —OZ.
`—NZZ and —COOZ, Z and Z denoting, independently of
`each other, a hydrogen atom or a linear Saturated C1-C6 or
`unsaturated C2-C6, or branched saturated or unsaturated
`C3-C6 hydrocarbon-based radical; and
`0043 the salts, optical isomers and solvates thereof.
`0044) These compounds are described especially in patent
`application FR 2899584 filed by L'Oréal.
`0045. A hydrocarbon-based radical is advantageously a
`saturated or unsaturated, linear or branched alkyl radical.
`Among the alkyl groups that are Suitable for use in the inven
`tion, mention may be made especially of methyl, ethyl, iso
`
`propyl. n-propyl. n-butyl, t-butyl, isobutyl, Sec-butyl, pentyl,
`n-hexyl, cyclopropyl, cyclopentyl, cyclohexyl and allyl
`groups.
`0046 More preferentially, use is made of compounds of
`formula (I) for which: R1 and R2 form, together with the
`oxygen atoms to which they are attached, an isopropylidene
`radical, R3 denotes: a group —COR4 with R4 denoting a
`linear C1-C9 hydrocarbon-based radical; or a biotin-based
`ester group.
`0047. 2',3'-Isopropylidene-5'-acetyladenosine is a known
`compound, which is described especially in patent applica
`tion WO-A-2004/037 159 (compound 265, page 203) in a
`pharmaceutical composition for treating obesity. The said
`document does not describe the application of the composi
`tion topically to the skin, especially for treating wrinkles.
`0048. Some of the compounds of formula (I) are known in
`the prior art and described in the following documents:
`0049. WO-A-2004/037159;
`0050 Poppe, Let al.: “Synthesis and characterization of
`(5'-deoxyadenosin-5-yl)cobalamin (="adenosylcobalamin)
`analogues mimicking the transition-state geometry of coen
`Zyme-B12-dependent rearrangements'; Helvetica Chimica
`Acta (1993), 76(6), 2367-83;
`0051 Jones, A. S. et al.: “Synthetic analogues of poly
`nucleotides. VII. Syntheses of 5'-O-acryloylnucleosides and
`copolymers of these with other acryloyl compounds': Journal
`of the Chemical Society Section C: Organic (1971), (19),
`3183-7;
`0.052 Mornet, D. et al.: “The reaction of myosin with a
`bromoalkyl analogue of adenosine 40 triphosphate’: FEBS
`Letters (1977), 84(2), 362-6: 4 25 30 Huber Gerhard;
`'esters of adenosine with organic and inorganic acids;
`Chem. Ber. 89,2853-62 (1956) ref CA52:2027g.
`0053 Takemoto, K. et al.: “Nucleic acid analogues: their
`specific interaction and applicability”; 5 Polymeric Materials
`Science and Engineering (1988), 58, 250-3:
`0054 Purkayastha, Bhupesh C.; Bhattacharyya, S. N:
`“Use of Ca oxalate monohydrate in the investigation of rare
`earth and thorium activities'; J. Indian. Chem. Soc. 34, 427
`33 (1957) ref. CA52:2627h;
`0055 Peterli, Stefan et al.: “Nitrostyrene derivatives of
`adenosine 5'-glutarates as selective inhibitors of the epider
`mal growth factor receptor protein tyrosine kinase': Hel
`vetica Chimica Acta (1992). 75(3), 696–706.
`0056. As compounds of formula (I), mention may be made
`especially of the following compounds: 2',3'-isopropylidene
`5'-butanoyladenosine,
`2',3'-isopropylidene-5'-octanoylad
`enosine, 2',3'-isopropylidene-5'-biotinoyl-adenosine, 2',3'-
`isopropylidene-5'-ethyladenosine,
`2',3'-isopropylidene-5'-
`octyladenosine,
`2',3'-dimethyl-5'-ethyladenosine,
`2',3'-
`dimethyl-5'-butanoyl-adenosine, or 2',3'-isopropylidene-5'-
`acetyladenosine (CAS No. 15888-38-7).
`0057 Adenosine is preferred in the present invention. It is
`especially commercially available in powder form from the
`company Pharma Waldhof.
`0058. The present invention also relates to the use of a
`composition according to the invention as defined previously,
`administered orally, topically or via cutaneous injection,
`especially for skin and/or scalp care.
`0059 A composition in accordance with the invention as
`defined previously may especially be a cosmetic composition
`for haircare, in particular for stimulating hair growth, com
`bating hair loss, slowing down hair loss or reinforcing the
`radiance of the hair.
`0060 Another object of the present invention is a treat
`ment method, in particular a cosmetic or therapeutic method,
`for reducing or preventing the signs of ageing of the skin or its
`
`

`

`US 2010/01 68049 A1
`
`Jul. 1, 2010
`
`integuments (hair, eyelashes, nails, etc.), by administration to
`an individual, preferably a human being, of an effective
`amount of at least one monosaccharide as defined previously
`in combination with an effective amount of at least one addi
`tional compound as defined previously. A Subject of the
`invention is in particular a cosmetic process for treating
`wrinkled skin, in particular the skin of the face and/or the
`forehead, comprising the topical application to the said skin
`of a composition comprising, in a physiologically acceptable
`medium, a combination of an effective amount of at least one
`monosaccharide as defined previously and of an effective
`amount of at least one additional compound as defined pre
`viously.
`0061 The composition according to the invention is more
`particularly intended to be applied to the areas of the body, the
`face or the forehead marked with wrinkles, and/or to people
`with wrinkles.
`0062. The present invention also relates to the use of the
`compositions or of the combination according to the inven
`tion for reducing and/or preventing the signs of ageing of the
`skin or its integuments, and in particular for reducing and/or
`preventing skin wrinkles.
`0063 Wrinkles include expression wrinkles and those
`caused by ageing. The expression wrinkles are preferably
`chosen from: crow's feet wrinkles, the nasal grooves,
`wrinkles between the eyebrows and wrinkles on the forehead.
`0064. The composition or combination according to the
`invention also makes it possible to stimulate the regeneration
`of epidermal and dermal cells, in the skin or the integuments,
`in particular keratinocytes and fibroblasts, particularly by
`increasing their proliferation. This therefore provides a
`method, especially a cosmetic method, which is especially
`effective for combating the signs of chronological ageing
`and/or photoageing.
`0065. The signs of photoageing correspond to internal
`degradations of the skin due to exposure to ultraviolet radia
`tion (actinic ageing). The signs of chronological ageing cor
`respond to internal degradations of the skin due to the intrin
`sic ageing of the individuals.
`0066. According to one preferred embodiment, the use
`according to the present invention is intended for improving
`the radiance of the complexion, for reducing and/or prevent
`ing the characteristics of wrinkles and/or fine lines, for
`improving and/or reducing the microrelief of the skin, and/or
`for making the skin Smooth and/or for improving the
`mechanical properties of the skin and/or for relaxing or
`decontracting the dermal contractile cells involved in the
`generation of expression wrinkles.
`0067. According to another aspect of the invention, the use
`of the composition or of the combination according to the
`invention makes it possible to improve the density of the skin,
`its firmness and/or the cohesion of its various compartments,
`in particular the cohesion of the dermis with the epidermis.
`0068. The present invention also relates to the use of the
`composition or combination according to the invention for
`preventively or curatively treating wrinkles and/or fine lines,
`withered skin, lack of skin elasticity and/or tonicity, thinning
`of the dermis, degradation of collagen fibres, flaccid skin,
`thinned skin and/or any internal degradation of the skin
`caused by exposure to ultraviolet radiation.
`0069. The present invention also relates to the use of the
`composition or combination according to the invention for
`decontracting the skin and/or relaxing the lines of the skin.
`0070 The compositions or the combination according to
`the invention also have the effect of increasing the synthesis
`of collagens, preferably procollagen I.
`
`0071. The amount of active ingredients, chosen from
`monosaccharides and adenosine and analogues as defined
`previously, to be used according to the invention depends on
`the desired cosmetic or therapeutic effect, and may thus vary
`within a wide range. A person skilled in the art can, on the
`basis of his general knowledge, readily determine the appro
`priate amounts.
`0072 Thus, and according to one preferred embodiment,
`the composition according to the invention comprises at least
`one monosaccharide as defined above in an amount of
`between 0.001% and 30% by weight relative to the total
`weight of the composition, and in particular between 0.1%
`and 10% by weight and more particularly between 0.5% and
`6% by weight relative to the total weight of the composition.
`0073. According to another preferred embodiment, the
`composition according to the invention comprises at least one
`monosaccharide as defined above in an amount of between
`1% and 10% by weight, and more particularly between 1%
`and 6% by weight relative to the total weight of the compo
`sition.
`0074 According to one preferred embodiment, the com
`position according to the invention comprises adenosine and/
`or at least one analogue thereof in an amount of between
`0.001% and 10% by weight relative to the total weight of the
`composition, in particular between 0.01% and 3% by weight,
`and more particularly between 0.01% and 1% by weight
`relative to the total weight of the composition.
`0075 According to another preferred embodiment, the
`composition according to the invention comprises adenosine
`and/or at least one analogue thereof in an amount of between
`0.01% and 10% by weight relative to the total weight of the
`composition, and in particular between 0.01% and 2% by
`weight relative to the total weight of the composition.
`0076. The monosaccharides, and the adenosine, a deriva
`tive thereof or analogues thereof, present in the composition
`defined above are active agents of the composition.
`(0077. The terms “active agent” and “active ingredient”
`more specifically mean according to the invention a com
`pound which, when administered to an individual, in particu
`lar a human individual, plays a direct biological role on the
`body, in particular on the skin or its integuments, in particular
`without improving the biological or mechanical effect of
`another compound present in the composition according to
`the invention.
`0078 Preferably, the composition according to the present
`invention also comprises at least one magnesium salt and at
`least one potassium salt.
`0079 A combination of adenosine with a magnesium salt
`and a potassium salt has been described in patent application
`EP 1428 522.
`0080. The magnesium and potassium salts that may be
`mentioned are the organic and inorganic salts of these metals.
`0081
`Examples of organic magnesium and potassium
`salts include the salts formed from a counteranion chosen
`from: a citrate, oxalate, acetate, gluconate, lactate, tartrate,
`maleate, benzoate, propionate, salicylate, ascorbate, formate,
`Succinate, folinate, aspartate, phthalate, oleate, palmitate,
`Stearate, lauryl Sulfate, lanolate, myristate, behenate, casein
`ate, cyclamate, pantothenate, polyaminopolycarboxylate,
`thioglycolate, laurate, ricinoleate, pidolate, Sorbate or glycyr
`rhizinate anion.
`0082 Examples of inorganic magnesium and potassium
`salts include the salts formed from a counteranion chosen
`from: a nitrate, Sulfate, halide, carbonate, bicarbonate,
`hydroxide, peroxide, nitride, sulfide, bisulfate, persulfate,
`glycerophosphate, hypophosphate or borate anion. The mag
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`US 2010/01 68049 A1
`
`Jul. 1, 2010
`
`nesium sulfate and dipotassium glycyrrhizinate are preferred
`for use in the present invention.
`0083. The amounts of adenosine and salts that may be
`introduced into the composition according to the invention
`may vary within a wide range as a function of the desired
`effect. By way of example, the magnesium salt may represent
`from 0.001% to 1% and preferably from 0.01% to 0.1% of the
`total weight of the composition. The potassium salt may
`represent from 0.001% to 1% and preferably from 0.01% to
`0.1% of the total weight of the composition.
`0084. The present invention relates especially to one of the
`compositions as defined previously, Suitable for topical
`administration to the skin or its integuments, oral administra
`tion or cutaneous injection.
`0085. The present invention also relates to a composition
`according to the invention, which is suitable for topical
`administration, advantageously in the form of a cream, a gel.
`a lotion, a milk, an oil, an ointment, a wax, a mousse, a paste,
`a serum, a pomade or a shampoo.
`I0086. When the composition according to the present
`invention is administered orally, it may advantageously be in
`the form of a gel capsule, a tablet or pills. When the compo
`sition according to the present invention is administered via
`cutaneous injection, it may in particular be in the form of a
`sterile solution.
`0087. In general, the medium in which the active prin
`ciples of the composition as defined previously are included is
`a physiologically acceptable medium, in particular a cosmeti
`cally or pharmaceutically acceptable medium, and may be
`anhydrous or aqueous. It may thus comprise an aqueous
`phase and/or a fatty phase.
`0088. The physiologically acceptable medium in which
`the compounds according to the invention may be employed,
`and also the constituents thereof, their amount, the galenical
`form of the composition, its mode of preparation and its mode
`of administration, may be chosen by a person skilled in the art
`on the basis of his general knowledge, as a function of the
`desired type of composition.
`0089. When the composition is a composition intended for
`topical administration, it may advantageously be in the form
`of aqueous or aqueous-alcoholic solutions, oil-in-water
`(O/W) or water-in-oil (W/O) emulsions or multiple emul
`sions (triple: W/O/W or O/W/O), nanoemulsions, in particu
`lar O/W nanoemulsions, in which the size of the drops is less
`than 100 nm, aqueous gels, or dispersions of a fatty phase in
`an aqueous phase with the aid of spherules, these spherules
`possibly being polymer nanoparticles such as nanospheres
`and nanocapsules or lipid vesicles of ionic and/or nonionic
`type (l